1. Field of the Invention
This invention is directed to new organic compounds and more specifically to 2-[2-(hydroxymethyl)imidazo-1-yl]benzophenones and 2-[2-(phthalimidomethyl)imidazo-1-yl]benzophenones and a process therefor.
The novel compound and the process of production therefor can be illustratively represented as follows: ##SPC4##
Wherein R.sub.0 and R.sub.1 are hydrogen or aklyl of 1 to 3 carbon atoms, inclusive; wherein R.sub.2 is hydrogen, chloro, fluoro, or trifluoromethyl; wherein R.sub.3 is hydrogen, or fluoro with the proviso that R.sub.3 is not fluoro, if R.sub.2 is chloro or trifluoromethyl; and wherein R.sub.4 is hydrogen, fluoro, chloro, bromo, nitro, or trifluoromethyl.
The process of this invention comprises: heating a compound of formula I with aqueous formalin with or without an organic inert solvent or paraformaldehyde in toluene or xylene or diglyme to a temperature between 100.degree. to 160.degree. C. to obtain the corresponding compound II; and treating II with triphenylphosphine, phthalimide and finally diethyl azodicarboxylate at -10.degree. to 15.degree. C. in an inert organic solvent such as tetrahydrofuran to give the corresponding compound III.
2. Description of the Preferred Embodiment
Alkyl groups of 1 to 3 carbon atoms inclusive are methyl, ethyl, propyl, and isopropyl.
The more preferred compounds II of this invention have the specific formula IIA: ##SPC5##
wherein R'.sub.0 and R'.sub.1 are hydrogen or methyl; wherein R'.sub.2 is hydrogen, chloro, or fluoro; wherein R'.sub.3 is hydrogen, or fluoro with the proviso that R'.sub.3 is not fluoro if R'.sub.2 is chloro; wherein R'.sub.4 is hydrogen, chloro, fluoro, or trifluoromethyl.
The most preferred compounds II of this invention have the specific formula IIB: ##SPC6##
wherein R'.sub.1 is hydrogen or methyl; wherein R".sub.2 is hydrogen or chloro; wherein R".sub.4 is hydrogen, chloro, or fluoro.
The more preferred compounds III have the specific formula IIIA ##SPC7##
wherein R'.sub.1 is hydrogen or methyl; wherein R'.sub.2 is hydrogen, chloro, or fluoro; wherein R'.sub.3 is hydrogen or fluoro with the proviso that R'.sub.3 is not fluoro if R'.sub.2 is chloro; wherein R'.sub.4 is hydrogen, chloro, fluoro, or trifluoromethyl.
The most preferred compounds of generic formula III have the specific formula IIIB ##SPC8##
wherein R'.sub.1 is hydrogen or methyl; wherein R".sub.2 is hydrogen or chloro; wherein R".sub.4 is hydrogen, chloro, or fluoro.
The compound of formulae II (including IIA and IIB) and of formula III (including IIIA and IIIB) are useful as intermediates for the production of 6-phenyl-4H-imidazo-[1,2-a][1,4]benzodiazepines IV by a scheme shown below: ##SPC9##
The activity of compounds of formula IV as tranquilizers sedatives and muscle relaxants is discussed in Belgian Patent No. 768,781, granted Feb. 5, 1973 or in South African Patent No. 72/4880 sealed October 1973.
The imidazobenzophenones of formula I are prepared as shown in the preparations.
In carrying out the process of this invention a selected starting compound of formula I is reacted with paraformaldehyde in a suitable inert organic solvent e.g. xylene, toluene, diglyme, or with an aqueous solution of formaldehyde such as commercial 37% aqueous formaldehyde (formalin) in a bomb at 1-20 atmosphere at 100.degree. to 170.degree. C. during a period of 1-12 hours. Thereafter the reaction mixture is quenched in an aqueous base e.g. sodium, potassium or barium hydroxide or sodium or potassium carbonate or bicarbonate and the product II is isolated and purified by conventional procedures e.g. extraction, chromatography, crystallization, and the like.
Compound II is then treated in a suspension of an inert organic solvent with phthalimide and triphenylphosphine. The inert solvent is usually tetrahydrofuran, monoglyme, diglyme or triglyme. In the preferred embodiment of this invention the phthalimide and triphenylphosphine are used in excess of 5-25% above the mol equivalent of compound II and the reaction is carried out between -10.degree. to 15.degree. C. during 1/2 to 2 hours. Thereafter, at a temperature of 0.degree. to 5.degree. C. the reaction mixture is treated dropwise with diethyl azodicarboxylate using the equimolar amount in which the phthalimide above was used. The addition is carried out under continuous stirring during 1/2 to 2 hours and thereafter the stirring is continued for 8-24 hours permitting the solution to warm to room temperature (20.degree.-30.degree. C.). After this period the reaction is terminated and the product III, thus obtained, is isolated and purified by conventional means such as extraction, filtration, chromatography and/or crystallization.
The following preparations and examples are illustrative of the processes and products of the present invention, but are not to be construed as limiting.